[Federal Register Volume 87, Number 73 (Friday, April 15, 2022)]
[Notices]
[Pages 22537-22539]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-08114]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-4367]


Bioavailability Studies Submitted in NDAs or INDs--General 
Considerations; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled 
``Bioavailability Studies Submitted in NDAs or INDs--General 
Considerations.'' This guidance provides recommendations to sponsors 
planning to include bioavailability (BA) information for drug products 
in investigational new drug applications (INDs), new drug applications 
(NDAs), and NDA supplements. This guidance finalizes the draft guidance 
of the same title issued on February 26, 2019. This guidance also 
replaces the draft guidance entitled ``Bioavailability and 
Bioequivalence Studies Submitted in NDAs or INDs--General 
Considerations'' issued March 2014.

DATES: The announcement of the guidance is published in the Federal 
Register on April 15, 2022.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your

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comment does not include any confidential information that you or a 
third party may not wish to be posted, such as medical information, 
your or anyone else's Social Security number, or confidential business 
information, such as a manufacturing process. Please note that if you 
include your name, contact information, or other information that 
identifies you in the body of your comments, that information will be 
posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-D-4367 for ``Bioavailability Studies Submitted in NDAs or 
INDs--General Considerations.'' Received comments will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Dakshina Chilukuri, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-1515, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Bioavailability Studies Submitted in NDAs or INDs--General 
Considerations.'' Determining the BA of formulations is critical during 
the life cycle of drug products and aids in the FDA's evaluation of the 
safety and effectiveness of a product in INDs, NDAs, or NDA 
supplements. This guidance provides recommendations to sponsors and 
applicants planning to include BA information for drug products in 
INDs, NDAs, and NDA supplements. This guidance contains recommendations 
on how to meet the BA requirements set forth in part 320 (21 CFR part 
320) as they apply to dosage forms intended for oral administration. 
The guidance is also applicable to non-orally administered drug 
products when it is appropriate to rely on systemic exposure measures 
to determine the BA of a drug (e.g., transdermal delivery systems and 
certain rectal and nasal drug products). The guidance provides 
recommendations on conducting relative BA studies during the 
investigational period for an NDA and bioequivalence (BE) studies 
during the postapproval period for certain changes to drug products 
with an approved NDA.
    This guidance finalizes the draft guidance entitled 
``Bioavailability Studies in NDAs or INDs--General Considerations'' 
issued on February 26, 2019 (84 FR 6148) (the 2019 draft guidance). 
When FDA issued the 2019 draft guidance, FDA explained that the 2019 
draft guidance revised and replaced the draft guidance entitled 
``Bioavailability and Bioequivalence Studies Submitted in NDAs or 
INDs--General Considerations'' issued on March 2014 (the 2014 draft 
guidance) (84 FR 6148). FDA considered comments received on the 2014 
draft guidance in preparing the 2019 draft guidance. FDA likewise 
considered comments received on the 2019 draft guidance as this 
guidance was finalized. Changes from the 2019 draft guidance to the 
final guidance include the following: (1) Specifying that individual 
pharmacokinetic profiles will be considered for products with complex 
release characteristics; (2) clarifying that if the drug labeling 
specifies the drug to be taken with food but does not elaborate on the 
fed conditions, the sponsor should use a high-fat meal as the fed 
condition; (3) adding statistical approaches for dissolution; (4) 
clarifying that enzymes can be added to the dissolution medium to 
better understand the effect of over-encapsulation on drug release; and 
(5) removing the 10 percent alcohol level for dose-dumping studies. In 
addition, editorial changes were made to improve clarity.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Bioavailability Studies in NDAs or INDs--
General Considerations.'' It does not establish any rights for any 
person and is not binding on FDA or the public. You can use an 
alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.

[[Page 22539]]

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA.
    The collections of information in 21 CFR part 314 relating to the 
submission of new drug applications, abbreviated new drug applications, 
and supplemental applications and the submission of requests to waive 
in vivo BA and BE requirements have been approved under OMB control 
number 0910-0001.
    The collections of information in 21 CFR part 312 relating to the 
submission of investigational new drug applications and BA/BE studies 
or pharmacogenomic data and the collections of information in part 320 
for drug safety reporting have been approved under OMB control numbers 
0910-0014 and 0910-0291.
    The collections of information in 21 CFR parts 50 and 56 relating 
to the protection of human subjects and investigational review boards 
have been approved under OMB control number 0910-0130.
    The collections of information in 21 CFR 201.56 and 201.57 for the 
Requirements on Content and Format of Labeling for Human Prescription 
Drug and Biological Products have been approved under OMB control 
number 0910-0572.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.regulations.gov, or https://www.fda.gov/regulatory-information/search-fda-guidance-documents.

    Dated: April 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08114 Filed 4-14-22; 8:45 am]
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